An NIR-Ⅱ-absorbing Photothermal Agent Containing Multiple Rotors For Tumor Imaging And Therapy

Malignant tumors,as one of the main causes of human death,seriously threaten human health and life worldwide.Phototherapy,also known as optical diagnosis and treatment,is a new diagnosis and treatment mode that utilizes the photoactivated excited state energy conversion effect to realize disease diagnosis and in situ treatment.Due to its advantages of high sensitivity,non-invasive,and low side effects,it meets the current requirements for tumor imaging diagnosis and treatment technology in the biomedical field.Photothermal therapy,as one of the new cancer treatment techniques,has received extensive attention owing to its high efficiency in tumor elimination and minimal damage to normal tissue.Photothermal agents,the key to the efficacy of photothermal therapy,can convert light energy into heat within tumor tissue.This locally generated heat results in cell membrane destruction and protein denaturation,thus achieving the goal of tumor therapy.At the same time,this heat can also be used for photoacoustic imaging and photothermal imaging.This property leads to the photothermal agent itself,also acting as a phototherapeutic agent to simultaneously image and ablate the tumor by a single injection and irradiation.At present,there are still some problems in the application of photothermal therapy in clinical practice,and an effective solution is to design NIR-II photothermal materials.In this thesis,through reasonable design and development of phototherapeutic agents with the absorption of NIR-II region,its imaging and therapeutic effects on tumors are explored.The specific research contents of this thesis are shown as follows:Part One:By adjusting the photothermal properties of molecules through reasonable molecular design,the second near-infrared photothermal agent raw material molecule BBTD-TP with multiple rotors was synthesized.The synthesized molecules were characterized by NMR and mass spectrometry,and the molecular structure was determined.The optical properties of the molecules were characterized by UV-Vis absorption spectrometer and fluorescence emission spectrometer.It laid a foundation for the preparation of organic small-molecule photothermal agents absorbed in the second near-infrared window.Part Two:In this chapter,BBTD-TP was encapsulated by the amphiphilic polymer DSPE-PEG₂₀₀₀-OH to ensure compatibility with a biological environment.Then,the optical properties,particle size,and morphology of the nanoparticles were characterized,and the drug loading rate was determined.NPs had excellent photostability and resistance to photobleaching.NPs showed high photothermal conversion performance under 808 nm and 1064 nm laser irradiation.Especially under 1064 nm laser irradiation,NPs had better imaging and therapeutic potential.BBTD-TP NPs showed good cell uptake capacity,biosafety,and phototoxicity in-vitro cell experiments,and showed high-quality imaging effects and efficient tumor thermal ablation ability in the nude mouse xenograft model.